The long term objectives of this proposal are to develop and refine methods of breast cancer staging in patients that are substantially less morbid than current methods, yet still provide the same diagnostic and therapeutic benefits. For the past six years, in partnership with the National Surgical Adjuvant Breast and Bowel cooperative group (NSABP), we have been conducting a large, multi-center, randomized, phase III prospective trial to compare sentinel node resection to conventional axillary dissection in clinically node-negative breast cancer patients. The University of Vermont (UVM) and NSABP share responsibility for overall trial design, protocol development, and statistical analysis. UVM has primary responsibility for 1) training and quality control of all aspects of sentinel node surgery and the pathological evaluation of sentinel nodes and 2) performance and statistical analysis of an ancillary pathology study for detection and determination of the prognostic significance of "occult" node metastases. The scope of this competing continuation proposal includes 1) continuation of the existing sentinel node trial and 2) an additional ancillary study evaluating highly promising prognostic methods. The additional ancillary study will be structured on the same successful partnership of UVM and NSABP and will include evaluation of bone marrow micrometastases. The specific aims are #1 and #2) determine whether sentinel node resection alone compared to axillary dissection plus sentinel node resection results in equivalent long-term control of regional disease (Aim 1) and disease free and overall survival (Aim 2), aim #3 and #4 determine the magnitude of morbidity reduction (Aim 3) and improved quality of life (Aim 4) of sentinel node resection versus axillary resection, aim #5 determine whether immunohistochemical (IHC) analysis of hematoxylin and eosin (H&E) negative sentinel nodes identifies patients at risk for decreased overall and disease free survival, aim #6 establish a standardized method of sentinel node surgery in a large number of centers, and aim #7 determine the comparative effectiveness of bone marrow micrometastases for predicting the survival of breast cancer patients. [unreadable] [unreadable]